1.
Pfam
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Pfam is a database of protein families that includes their annotations and multiple sequence alignments generated using hidden Markov models. The most recent version, Pfam 31.0, was released in March 2017, the general purpose of the Pfam database is to provide a complete and accurate classification of protein families and domains. Originally, the rationale behind creating the database was to have a method of curating information on known protein families to improve the efficiency of annotating genomes. The Pfam classification of families has been widely adopted by biologists because of its wide coverage of proteins. Early genome projects, such as human and fly used Pfam extensively for functional annotation of genomic data, the Pfam website allows users to submit protein or DNA sequences to search for matches to families in the database. If DNA is submitted, a translation is performed, then each frame is searched. Family is the class, which simply indicates that members are related. Domains are defined as a structural unit or reusable sequence unit that can be found in multiple protein contexts. Repeats are not usually stable in isolation, but rather are required to form tandem repeats in order to form a domain or extended structure. Motifs are usually shorter sequence units found outside of globular domains, the descriptions of Pfam families are managed by the general public using Wikipedia. As of release 29.0,76. 1% of protein sequences in UniprotKB matched to at least one Pfam domain, new families come from a range of sources, primarily the PDB and analysis of complete proteomes to find genes with no Pfam hit. For each family, a subset of sequences are aligned into a high-quality seed alignment. Sequences for the alignment are taken primarily from pfamseq with some supplementation from UniprotKB. This seed alignment is used to build a profile hidden Markov model using HMMER. This HMM is then searched against sequence databases, and all hits that reach a curated gathering threshold are classified as members of the protein family, the resulting collection of members is then aligned to the profile HMM to generate a full alignment. For each family, a curated gathering threshold is assigned that maximises the number of true matches to the family while excluding any false positive matches. False positives are estimated by observing overlaps between Pfam family hits that are not from the same clan and this threshold is used to assess whether a match to a family HMM should be included in the protein family. Upon each update of Pfam, gathering thresholds are reassessed to prevent overlaps between new and existing families, domains of Unknown Function represent a growing fraction of the Pfam database
2.
InterPro
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The contents of InterPro consist of diagnostic signatures and the proteins that they significantly match. The signatures consist of models which describe protein families, domains or sites, models are built from the amino acid sequences of known families or domains and they are subsequently used to search unknown sequences in order to classify them. Each of the databases of InterPro contribute towards a different niche, from very high-level. InterPros intention is to provide a one-stop-shop for protein classification, where all the signatures produced by the different member databases are placed into entries within the InterPro database. Signatures which represent equivalent domains, sites or families are put into the same entry, additional information such as a description, consistent names and Gene Ontology terms are associated with each entry, where possible. InterPro contains three main entities, proteins, signatures and entries, the proteins in UniProtKB are also the central protein entities in InterPro. Information regarding which signatures significantly match these proteins are calculated as the sequences are released by UniProtKB, only signatures deemed to be of sufficient quality are integrated into InterPro. InterPro also includes data for splice variants and the contained in the UniParc. The signatures from InterPro come from 11 member databases, which are listed below, cATH-Gene3D describes protein families and domain architectures in complete genomes. Protein families are formed using a Markov clustering algorithm, followed by multi-linkage clustering according to sequence identity, mapping of predicted structure and sequence domains is undertaken using hidden Markov models libraries representing CATH and Pfam domains. Functional annotation is provided to proteins from multiple resources, functional prediction and analysis of domain architectures is available from the Gene3D website. HAMAP stands for High-quality Automated and Manual Annotation of microbial Proteomes, HAMAP profiles are manually created by expert curators they identify proteins that are part of well-conserved bacterial, archaeal and plastid-encoded proteins families or subfamilies. PANTHER is a collection of protein families that have been subdivided into functionally related subfamilies. Hidden Markov models are built for each family and subfamily for classifying additional protein sequences, Pfam is a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains and families. The primary PIRSF classification unit is the family, whose members are both homologous and homeomorphic. PRINTS is a compendium of protein fingerprints, a fingerprint is a group of conserved motifs used to characterise a protein family, its diagnostic power is refined by iterative scanning of UniProt. Usually the motifs do not overlap, but are separated along a sequence, ProDom domain database consists of an automatic compilation of homologous domains. Current versions of ProDom are built using a procedure based on recursive PSI-BLAST searches
3.
Protein Data Bank
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The Protein Data Bank is a crystallographic database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The PDB is overseen by a called the Worldwide Protein Data Bank. The PDB is a key resource in areas of structural biology, most major scientific journals, and some funding agencies, now require scientists to submit their structure data to the PDB. Many other databases use protein structures deposited in the PDB, for example, SCOP and CATH classify protein structures, while PDBsum provides a graphic overview of PDB entries using information from other sources, such as Gene ontology. By 1971, one of Meyers programs, SEARCH, enabled researchers to access information from the database to study protein structures offline. SEARCH was instrumental in enabling networking, thus marking the beginning of the PDB. Upon Hamiltons death in 1973, Tom Koeztle took over direction of the PDB for the subsequent 20 years, in January 1994, Joel Sussman of Israels Weizmann Institute of Science was appointed head of the PDB. In October 1998, the PDB was transferred to the Research Collaboratory for Structural Bioinformatics, the new director was Helen M. Berman of Rutgers University. In 2003, with the formation of the wwPDB, the PDB became an international organization, the founding members are PDBe, RCSB, and PDBj. Each of the four members of wwPDB can act as deposition, data processing, the data processing refers to the fact that wwPDB staff review and annotate each submitted entry. The data are automatically checked for plausibility. The PDB database is updated weekly, likewise, the PDB holdings list is also updated weekly. As of 14 March 2017, the breakdown of current holdings is as follows,103,514 structures in the PDB have a structure factor file,9,057 structures have an NMR restraint file. 2,826 structures in the PDB have a chemical shifts file, therefore, the final conformation of the protein is obtained, in the latter case, by solving a distance geometry problem. A few proteins are determined by cryo-electron microscopy, the significance of the structure factor files, mentioned above, is that, for PDB structures determined by X-ray diffraction that have a structure file, the electron density map may be viewed. The data of such structures is stored on the electron density server, however, since 2007, the rate of accumulation of new protein structures appears to have plateaued. The file format used by the PDB was called the PDB file format. This original format was restricted by the width of computer punch cards to 80 characters per line, around 1996, the macromolecular Crystallographic Information file format, mmCIF, which is an extension of the CIF format started to be phased in
4.
Entrez
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The name Entrez was chosen to reflect the spirit of welcoming the public to search the content available from the NLM. Entrez Global Query is a search and retrieval system that provides access to all databases simultaneously with a single query string. Entrez can efficiently retrieve related sequences, structures, and references, the Entrez system can provide views of gene and protein sequences and chromosome maps. Some textbooks are available online through the Entrez system. The Entrez front page provides, by default, access to the global query, all databases indexed by Entrez can be searched via a single query string, supporting boolean operators and search term tags to limit parts of the search statement to particular fields. This returns a unified results page, that shows the number of hits for the search in each of the databases, Entrez also provides a similar interface for searching each particular database and for refining search results. The Limits feature allows the user to narrow a search a web forms interface, the History feature gives a numbered list of recently performed queries. Results of previous queries can be referred to by number and combined via boolean operators, search results can be saved temporarily in a Clipboard. Users with a MyNCBI account can save queries indefinitely and also choose to have updates with new search results e-mailed for saved queries of most databases and it is widely used in the field of biotechnology as a reference tool for students and professionals alike. Entrez searches the following databases, PubMed, biomedical literature citations and abstracts, including Medline - articles from journals, in addition to using the search engine forms to query the data in Entrez, NCBI provides the Entrez Programming Utilities for more direct access to query results. The eUtils are accessed by posting specially formed URLs to the NCBI server, there was also an eUtils SOAP interface which was terminated on July 2015. In 1991, entrez was introduced in CD form, in 1993, a client-server version of the software provided connectivity with the internet. In 1994, NCBI established a website, and Entrez was a part of initial release. In 2001, Entrez bookshelf was released and in 2003, the Entrez Gene database was developed, Entrez search engine form Entrez Help
5.
National Center for Biotechnology Information
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The National Center for Biotechnology Information is part of the United States National Library of Medicine, a branch of the National Institutes of Health. The NCBI is located in Bethesda, Maryland and was founded in 1988 through legislation sponsored by Senator Claude Pepper, the NCBI houses a series of databases relevant to biotechnology and biomedicine and is an important resource for bioinformatics tools and services. Major databases include GenBank for DNA sequences and PubMed, a database for the biomedical literature. Other databases include the NCBI Epigenomics database, all these databases are available online through the Entrez search engine. NCBI is directed by David Lipman, one of the authors of the BLAST sequence alignment program. He also leads a research program, including groups led by Stephen Altschul, David Landsman, Eugene Koonin, John Wilbur, Teresa Przytycka. NCBI is listed in the Registry of Research Data Repositories re3data. org, NCBI has had responsibility for making available the GenBank DNA sequence database since 1992. GenBank coordinates with individual laboratories and other databases such as those of the European Molecular Biology Laboratory. Since 1992, NCBI has grown to other databases in addition to GenBank. The NCBI assigns a unique identifier to each species of organism, the NCBI has software tools that are available by WWW browsing or by FTP. For example, BLAST is a sequence similarity searching program, BLAST can do sequence comparisons against the GenBank DNA database in less than 15 seconds. RAG2/IL2RG The NCBI Bookshelf is a collection of freely accessible, downloadable, some of the books are online versions of previously published books, while others, such as Coffee Break, are written and edited by NCBI staff. BLAST is a used for calculating sequence similarity between biological sequences such as nucleotide sequences of DNA and amino acid sequences of proteins. BLAST is a tool for finding sequences similar to the query sequence within the same organism or in different organisms. It searches the query sequence on NCBI databases and servers and post the results back to the browser in chosen format. Input sequences to the BLAST are mostly in FASTA or Genbank format while output could be delivered in variety of such as HTML, XML formatting. HTML is the output format for NCBIs web-page. Entrez is both indexing and retrieval system having data from sources for biomedical research
6.
UniProt
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UniProt is a freely accessible database of protein sequence and functional information, many entries being derived from genome sequencing projects. It contains an amount of information about the biological function of proteins derived from the research literature. The UniProt consortium comprises the European Bioinformatics Institute, the Swiss Institute of Bioinformatics, EBI, located at the Wellcome Trust Genome Campus in Hinxton, UK, hosts a large resource of bioinformatics databases and services. SIB, located in Geneva, Switzerland, maintains the ExPASy servers that are a resource for proteomics tools. In 2002, EBI, SIB, and PIR joined forces as the UniProt consortium, each consortium member is heavily involved in protein database maintenance and annotation. Until recently, EBI and SIB together produced the Swiss-Prot and TrEMBL databases and these databases coexisted with differing protein sequence coverage and annotation priorities. Swiss-Prot aimed to provide reliable protein sequences associated with a level of annotation. Recognizing that sequence data were being generated at a pace exceeding Swiss-Prots ability to keep up, meanwhile, PIR maintained the PIR-PSD and related databases, including iProClass, a database of protein sequences and curated families. The consortium members pooled their resources and expertise, and launched UniProt in December 2003. UniProt provides four core databases, UniProtKB, UniParc, UniRef, UniProt Knowledgebase is a protein database partially curated by experts, consisting of two sections, UniProtKB/Swiss-Prot and UniProtKB/TrEMBL. As of 19 March 2014, release 2014_03 of UniProtKB/Swiss-Prot contains 542,782 sequence entries, UniProtKB/Swiss-Prot is a manually annotated, non-redundant protein sequence database. It combines information extracted from literature and biocurator-evaluated computational analysis. The aim of UniProtKB/Swiss-Prot is to all known relevant information about a particular protein. Annotation is regularly reviewed to keep up with current scientific findings, the manual annotation of an entry involves detailed analysis of the protein sequence and of the scientific literature. Sequences from the gene and the same species are merged into the same database entry. Differences between sequences are identified, and their cause documented, a range of sequence analysis tools is used in the annotation of UniProtKB/Swiss-Prot entries. Computer-predictions are manually evaluated, and relevant results selected for inclusion in the entry and these predictions include post-translational modifications, transmembrane domains and topology, signal peptides, domain identification, and protein family classification. Relevant publications are identified by searching databases such as PubMed, the full text of each paper is read, and information is extracted and added to the entry
7.
Chromosome
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A chromosome is a DNA molecule with part or all of the genetic material of an organism. Prokaryotes usually have one single circular chromosome, whereas most eukaryotes are diploid, chromosomes in eukaryotes are composed of chromatin fiber. Chromatin fiber is made of nucleosomes, a nucleosome is a histone octamer with part of a longer DNA strand attached to and wrapped around it. Chromatin fiber, together with associated proteins is known as chromatin, chromatin is present in most cells, with a few exceptions, for example, red blood cells. Occurring only in the nucleus of cells, chromatin contains the vast majority of DNA, except for a small amount inherited maternally. Chromosomes are normally visible under a microscope only when the cell is undergoing the metaphase of cell division. Before this happens every chromosome is copied once, and the copy is joined to the original by a centromere resulting in an X-shaped structure, the original chromosome and the copy are now called sister chromatids. During metaphase, when a chromosome is in its most condensed state, in this highly condensed form chromosomes are easiest to distinguish and study. In prokaryotic cells, chromatin occurs free-floating in cytoplasm, as these cells lack organelles, the main information-carrying macromolecule is a single piece of coiled double-helix DNA, containing many genes, regulatory elements and other noncoding DNA. The DNA-bound macromolecules are proteins that serve to package the DNA, chromosomes vary widely between different organisms. Some species such as certain bacteria also contain plasmids or other extrachromosomal DNA and these are circular structures in the cytoplasm that contain cellular DNA and play a role in horizontal gene transfer. Chromosomal recombination during meiosis and subsequent sexual reproduction plays a significant role in genetic diversity. In prokaryotes and viruses, the DNA is often densely packed and organized, in the case of archaea, by homologs to eukaryotic histones, small circular genomes called plasmids are often found in bacteria and also in mitochondria and chloroplasts, reflecting their bacterial origins. Some use the term chromosome in a sense, to refer to the individualized portions of chromatin in cells. However, others use the concept in a sense, to refer to the individualized portions of chromatin during cell division. The word chromosome comes from the Greek χρῶμα and σῶμα, describing their strong staining by particular dyes, schleiden, Virchow and Bütschli were among the first scientists who recognized the structures now so familiar to everyone as chromosomes. The term was coined by von Waldeyer-Hartz, referring to the term chromatin, in a series of experiments beginning in the mid-1880s, Theodor Boveri gave the definitive demonstration that chromosomes are the vectors of heredity. His two principles were the continuity of chromosomes and the individuality of chromosomes and it is the second of these principles that was so original
8.
Bacteria
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Bacteria constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a number of shapes, ranging from spheres to rods, Bacteria were among the first life forms to appear on Earth, and are present in most of its habitats. Bacteria inhabit soil, water, acidic hot springs, radioactive waste, Bacteria also live in symbiotic and parasitic relationships with plants and animals. Most bacteria have not been characterised, and only half of the bacterial phyla have species that can be grown in the laboratory. The study of bacteria is known as bacteriology, a branch of microbiology, There are typically 40 million bacterial cells in a gram of soil and a million bacterial cells in a millilitre of fresh water. There are approximately 5×1030 bacteria on Earth, forming a biomass which exceeds that of all plants, Bacteria are vital in many stages of the nutrient cycle by recycling nutrients such as the fixation of nitrogen from the atmosphere. The nutrient cycle includes the decomposition of bodies and bacteria are responsible for the putrefaction stage in this process. In March 2013, data reported by researchers in October 2012, was published and it was suggested that bacteria thrive in the Mariana Trench, which with a depth of up to 11 kilometres is the deepest known part of the oceans. Other researchers reported related studies that microbes thrive inside rocks up to 580 metres below the sea floor under 2.6 kilometres of ocean off the coast of the northwestern United States. According to one of the researchers, You can find microbes everywhere—theyre extremely adaptable to conditions, the vast majority of the bacteria in the body are rendered harmless by the protective effects of the immune system, though many are beneficial particularly in the gut flora. However several species of bacteria are pathogenic and cause diseases, including cholera, syphilis, anthrax, leprosy. The most common fatal diseases are respiratory infections, with tuberculosis alone killing about 2 million people per year. In developed countries, antibiotics are used to treat infections and are also used in farming, making antibiotic resistance a growing problem. Once regarded as constituting the class Schizomycetes, bacteria are now classified as prokaryotes. Unlike cells of animals and other eukaryotes, bacterial cells do not contain a nucleus and these evolutionary domains are called Bacteria and Archaea. The ancestors of modern bacteria were unicellular microorganisms that were the first forms of life to appear on Earth, for about 3 billion years, most organisms were microscopic, and bacteria and archaea were the dominant forms of life. In 2008, fossils of macroorganisms were discovered and named as the Francevillian biota, however, gene sequences can be used to reconstruct the bacterial phylogeny, and these studies indicate that bacteria diverged first from the archaeal/eukaryotic lineage. Bacteria were also involved in the second great evolutionary divergence, that of the archaea, here, eukaryotes resulted from the entering of ancient bacteria into endosymbiotic associations with the ancestors of eukaryotic cells, which were themselves possibly related to the Archaea
9.
Gene
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A gene is a locus of DNA which is made up of nucleotides and is the molecular unit of heredity. The transmission of genes to an offspring is the basis of the inheritance of phenotypic traits. These genes make up different DNA sequences called genotypes, genotypes along with environmental and developmental factors determine what the phenotypes will be. Most biological traits are under the influence of polygenes as well as gene–environment interactions, genes can acquire mutations in their sequence, leading to different variants, known as alleles, in the population. These alleles encode slightly different versions of a protein, which cause different phenotypical traits, usage of the term having a gene typically refers to containing a different allele of the same, shared gene. Genes evolve due to natural selection or survival of the fittest of the alleles, the concept of a gene continues to be refined as new phenomena are discovered. For example, regulatory regions of a gene can be far removed from its coding regions, some viruses store their genome in RNA instead of DNA and some gene products are functional non-coding RNAs. The existence of discrete inheritable units was first suggested by Gregor Mendel, from 1857 to 1864, in Brno, he studied inheritance patterns in 8000 common edible pea plants, tracking distinct traits from parent to offspring. He described these mathematically as 2n combinations where n is the number of differing characteristics in the original peas, although he did not use the term gene, he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured the distinction between genotype and phenotype, charles Darwin developed a theory of inheritance he termed pangenesis, from Greek pan and genesis / genos. Darwin used the term gemmule to describe hypothetical particles that would mix during reproduction, de Vries called these units pangenes, after Darwins 1868 pangenesis theory. In 1909 the Danish botanist Wilhelm Johannsen shortened the name to gene, advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid was shown to be the repository of genetic information by experiments in the 1940s to 1950s. In the early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities, indivisible by recombination, collectively, this body of research established the central dogma of molecular biology, which states that proteins are translated from RNA, which is transcribed from DNA. This dogma has since shown to have exceptions, such as reverse transcription in retroviruses. The modern study of genetics at the level of DNA is known as molecular genetics, in 1972, Walter Fiers and his team at the University of Ghent were the first to determine the sequence of a gene, the gene for Bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing, an automated version of the Sanger method was used in early phases of the Human Genome Project. The theories developed in the 1930s and 1940s to integrate molecular genetics with Darwinian evolution are called the evolutionary synthesis
10.
Bacteriophage
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A bacteriophage /ˈbækˈtɪər. i. oʊˌfeɪdʒ/ is a virus that infects and replicates within a bacterium. The term is derived from bacteria and the Greek, φαγεῖν, bacteriophages are composed of proteins that encapsulate a DNA or RNA genome, and may have relatively simple or elaborate structures. Their genomes may encode as few as four genes, and as many as hundreds of genes, phages replicate within the bacterium following the injection of their genome into its cytoplasm. Bacteriophages are among the most common and diverse entities in the biosphere, phages are widely distributed in locations populated by bacterial hosts, such as soil or the intestines of animals. They have been used for over 90 years as an alternative to antibiotics in the former Soviet Union and Central Europe and they are seen as a possible therapy against multi-drug-resistant strains of many bacteria. Bacteriophages occur abundantly in the biosphere, with different virions, genomes, phages are classified by the International Committee on Taxonomy of Viruses according to morphology and nucleic acid. Nineteen families are recognized by the ICTV that infect bacteria. Of these, only two families have RNA genomes, and only five families are enveloped, of the viral families with DNA genomes, only two have single-stranded genomes. Eight of the families with DNA genomes have circular genomes while nine have linear genomes. Nine families infect bacteria only, nine infect archaea only, in 1915, British bacteriologist Frederick Twort, superintendent of the Brown Institution of London, discovered a small agent that infected and killed bacteria. He believed the agent must be one of the following, a stage in the cycle of the bacteria. Tworts work was interrupted by the onset of World War I, for d’Hérelle, there was no question as to the nature of his discovery, In a flash I had understood, what caused my clear spots was in fact an invisible microbe … a virus parasitic on bacteria. DHérelle called the virus a bacteriophage or bacteria-eater and he also recorded a dramatic account of a man suffering from dysentery who was restored to good health by the bacteriophages. It was DHerelle who conducted research into bacteriophages and introduced the concept of phage therapy. In 1969, Max Delbrück, Alfred Hershey and Salvador Luria were awarded the Nobel Prize in Physiology and Medicine for their discoveries of the replication of viruses and their genetic structure. Phages were discovered to be agents and were used in the former Soviet Republic of Georgia. They had widespread use, including treatment of soldiers in the Red Army, however, they were abandoned for general use in the West for several reasons, Medical trials were carried out, but a basic lack of understanding of phages made these invalid. Antibiotics were discovered and marketed widely and they were easier to make, store and to prescribe
11.
Peptide
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Peptides are biologically occurring short chains of amino acid monomers linked by peptide bonds. The covalent chemical bonds are formed when the group of one amino acid reacts with the amine group of another. The shortest peptides are dipeptides, consisting of 2 amino acids joined by a peptide bond, followed by tripeptides, tetrapeptides. A polypeptide is a long, continuous, and unbranched peptide chain, hence, peptides fall under the broad chemical classes of biological oligomers and polymers, alongside nucleic acids, oligosaccharides and polysaccharides, etc. Peptides are distinguished from proteins on the basis of size, all peptides except cyclic peptides have an N-terminal and C-terminal residue at the end of the peptide. Ribosomal peptides Ribosomal peptides are synthesized by translation of mRNA and they are often subjected to proteolysis to generate the mature form. These function, typically in higher organisms, as hormones and signaling molecules, some organisms produce peptides as antibiotics, such as microcins. Since they are translated, the amino acid residues involved are restricted to those utilized by the ribosome, however, these peptides frequently have posttranslational modifications such as phosphorylation, hydroxylation, sulfonation, palmitoylation, glycosylation and disulfide formation. In general, they are linear, although lariat structures have been observed, more exotic manipulations do occur, such as racemization of L-amino acids to D-amino acids in platypus venom. Nonribosomal peptides Nonribosomal peptides are assembled by enzymes that are specific to each peptide, the most common non-ribosomal peptide is glutathione, which is a component of the antioxidant defenses of most aerobic organisms. Other nonribosomal peptides are most common in organisms, plants. These complexes are often out in a similar fashion. These peptides are often cyclic and can have highly complex cyclic structures, since the system is closely related to the machinery for building fatty acids and polyketides, hybrid compounds are often found. The presence of oxazoles or thiazoles often indicates that the compound was synthesized in this fashion, Peptones See also Tryptone Peptones are derived from animal milk or meat digested by proteolysis. In addition to containing small peptides, the material includes fats, metals, salts, vitamins. Peptones are used in nutrient media for growing bacteria and fungi, Peptide fragments Peptide fragments refer to fragments of proteins that are used to identify or quantify the source protein. Peptides received prominence in molecular biology for several reasons, the first is that peptides allow the creation of peptide antibodies in animals without the need of purifying the protein of interest. This involves synthesizing antigenic peptides of sections of the protein of interest and these will then be used to make antibodies in a rabbit or mouse against the protein
12.
Protein subunit
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In structural biology, a protein subunit is a single protein molecule that assembles with other protein molecules to form a protein complex. Some naturally occurring proteins have a small number of subunits and therefore described as oligomeric. Others may consist from a large number of subunits and therefore described as multimeric, for example microtubules. The subunits of a protein may be identical, homologous or totally dissimilar. In some protein assemblies, one subunit may be a subunit that enzymatically catalyzes a reaction. Although telomerase has telomerase reverse transcriptase as a subunit, regulation is accomplished by factors outside of the protein. An enzyme composed of regulatory and catalytic subunits when assembled is often referred to as a holoenzyme. For example, class I phosphoinositide 3-kinase is composed of a catalytic subunit. One subunit is made of one polypeptide chain, a polypeptide chain has one gene coding for it – meaning that a protein must have one gene for each unique subunit. A subunit is often named with a Greek or Roman letter, for example, ATP synthase has a type of subunit called α. Three of these are present in the ATP synthase molecule, and is therefore designated α3, larger groups of subunits can also the specified, like α3β3-hexamer and c-ring. A subunit vaccine presents an antigen to the system without introducing viral particles. One method of production involves isolation of a protein from a virus. A weakness of this technique is that proteins can be denatured. The recombinant vector that is genomically modified will express the antigen, the antigen is extracted from the vector. Just like the highly successful subunit vaccines, the antigen will be of little to no risk to the patient. Vi capsular polysaccharide vaccine is another subunit vaccine, in this case and it is also called a conjugate vaccine, in which a polysaccharide antigen has been covalently attached to a carrier protein for T-cell-dependent antigen processing. Protein quaternary structure Allostery Cooperativity Monomer Dilip Gore, Reecha Pandit, in silico Identification of Cell Surface Antigens in Neisseria meningitidis
13.
Disulfide
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In chemistry, a disulfide refers to a functional group with the structure R–S–S–R. The linkage is called an SS-bond or sometimes a disulfide bridge and is usually derived by the coupling of two thiol groups. The connection is a persulfide, in analogy to its congener, peroxide, in inorganic chemistry disulfide usually refers to the corresponding anion S2−2, for example in disulfur dichloride. The disulfide bonds are strong, with a bond dissociation energy of 60 kcal/mol. However, being about 40% weaker than C–C and C–H bonds, rotation about the S–S axis is subject to a low barrier. Disulfides show a preference for dihedral angles approaching 90°. When the angle approaches 0° or 180°, then the disulfide is a significantly better oxidant, disulfides where the two R groups are the same are called symmetric, examples being diphenyl disulfide and dimethyl disulfide. When the two R groups are not identical, the compound is said to be an asymmetric or mixed disulfide, by comparison, the standard reduction potential for ferrodoxins is about −430 mV. Disulfide bonds are formed from the oxidation of sulfhydryl groups. The transformation is depicted as follows,2 RSH ⇌ RS–SR +2 H+ +2 e− A variety of oxidants promote this reaction including air, such reactions are thought to proceed via sulfenic acid intermediates. In the laboratory, iodine in the presence of base is employed to oxidize thiols to disulfides. Several metals, such as copper and iron complexes affect this reaction, the alkylation of alkali metal di- and polysulfides gives disulfides. Thiokol polymers arise when sodium polysulfide is treated with an alkyl dihalide, in the converse reaction, carbanionic reagents react with elemental sulfur to afford mixtures of the thioether, disulfide, and higher polysulfides. These reactions are often unselective but can be optimized for specific applications, many specialized methods have been developed for forming disulfides, usually for applications in organic synthesis. A variety of reductants can be used, furthermore, it is often not needed to remove TCEP before modification of protein thiols. In organic synthesis, hydride agents are employed for scission of disulfides. The original disulfide bond is broken, and its other sulfur atom is released as a new thiolate, meanwhile, a new disulfide bond forms between the attacking thiolate and the original sulfur atom. Thiolates, not thiols, attack disulfide bonds, hence, thiol–disulfide exchange is inhibited at low pH where the protonated thiol form is favored relative to the deprotonated thiolate form
14.
AB toxin
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The AB toxins are two-component protein complexes secreted by a number of pathogenic bacteria. They can be classified as Type III toxins because they interfere with internal cell function and they are named AB toxins due to their components, the A component is usually the active portion, and the B component is usually the binding portion. The A subunit possesses enzyme activity, and is transferred to the host cell following a change in the membrane-bound transport B subunit. Among the toxins produced by certain Clostridium spp. are the binary exotoxins and these proteins consist of two independent polypeptides, which correspond to the A/B subunit moieties. The enzyme component enters the cell through endosomes produced by the oligomeric binding/translocation protein, members of the A binary toxin family include C. perfringens iota toxin Ia, C. botulinum C2 toxin CI, and Clostridium difficile ADP-ribosyltransferase. Other homologous proteins have been found in Clostridium spiroforme, members of the B binary toxin family include the Bacillus anthracis protective antigen protein, The toxin comprises three factors, the protective antigen, the oedema factor, and the lethal factor. Each is a protein of ~80kDa. PA forms the B part of the exotoxin and allows passage of the A moiety into target cells, PA protein forms the central part of the complete anthrax toxin, and translocates the B moiety into host cells after assembling as a heptamer in the membrane. The Diphtheria toxin also is an AB toxin and it inhibits protein synthesis in the host cell through phosphorylation of the eukaryotic elongation factor 2, which is an essential component for protein synthesis. The exotoxin A of Pseudomonas aeruginosa is another example of an AB toxin that targets the eukaryotic elongation factor 2, the AB5 toxins are usually considered a type of AB toxin, characterized by B pentamers. Less commonly, the term AB toxin is used to emphasize the character of the B component. This article incorporates text from the public domain Pfam and InterPro IPR003540 This article incorporates text from the public domain Pfam and InterPro IPR003896
15.
Host (biology)
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In biology, a host is an organism that harbors a parasitic, a mutual, or a commensal symbiont, typically providing nourishment and shelter. Examples include animals playing host to parasitic worms, cells harbouring a parasitic virus, more specifically in botany, a host plant supplies food resources and acts as a substrate for commensalist insects or other fauna. Guest is the term used for parasites, mutualists and commensals. The host range of a parasite is the collection of hosts that an organism can utilize as a partner, in the case of human parasites, the host range influences the epidemiology of the parasitism or disease. For instance, the production of antigenic shifts in Influenza A virus can result from pigs being infected with the virus from different hosts. This co-infection provides an opportunity for mixing of the viral genes between existing strains, thereby producing a new viral strain
16.
Crystal structure
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In crystallography, crystal structure is a description of the ordered arrangement of atoms, ions or molecules in a crystalline material. Ordered structures occur from the nature of the constituent particles to form symmetric patterns that repeat along the principal directions of three-dimensional space in matter. The smallest group of particles in the material that constitutes the pattern is the unit cell of the structure. The unit cell completely defines the symmetry and structure of the crystal lattice. The repeating patterns are said to be located at the points of the Bravais lattice, the lengths of the principal axes, or edges, of the unit cell and the angles between them are the lattice constants, also called lattice parameters. The symmetry properties of the crystal are described by the concept of space groups, all possible symmetric arrangements of particles in three-dimensional space may be described by the 230 space groups. The crystal structure and symmetry play a role in determining many physical properties, such as cleavage, electronic band structure. The crystal structure of a material can be described in terms of its unit cell, the unit cell is a box containing one or more atoms arranged in three dimensions. The unit cells stacked in three-dimensional space describe the arrangement of atoms of the crystal. Commonly, atomic positions are represented in terms of fractional coordinates, the atom positions within the unit cell can be calculated through application of symmetry operations to the asymmetric unit. The asymmetric unit refers to the smallest possible occupation of space within the unit cell and this does not, however imply that the entirety of the asymmetric unit must lie within the boundaries of the unit cell. Symmetric transformations of atom positions are calculated from the group of the crystal structure. Vectors and planes in a lattice are described by the three-value Miller index notation. It uses the indices ℓ, m, and n as directional parameters, which are separated by 90°, by definition, the syntax denotes a plane that intercepts the three points a1/ℓ, a2/m, and a3/n, or some multiple thereof. That is, the Miller indices are proportional to the inverses of the intercepts of the plane with the unit cell, if one or more of the indices is zero, it means that the planes do not intersect that axis. A plane containing a coordinate axis is translated so that it no longer contains that axis before its Miller indices are determined, the Miller indices for a plane are integers with no common factors. Negative indices are indicated with horizontal bars, as in, in an orthogonal coordinate system for a cubic cell, the Miller indices of a plane are the Cartesian components of a vector normal to the plane. Likewise, the planes are geometric planes linking nodes
17.
Protein dimer
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In biochemistry, a dimer is a macromolecular complex formed by two, usually non-covalently bound, macromolecules such as proteins or nucleic acids. It is a structure of a protein. A homodimer is formed by two identical molecules, a heterodimer is formed by two different macromolecules. Most dimers in biochemistry are not connected by covalent bonds, an example of a non-covalent heterodimer is the enzyme reverse transcriptase, which is composed of two different amino acid chains. An exception is dimers that are linked by disulfide bridges such as the homodimeric protein NEMO, some proteins contain specialized domains to ensure dimerization
18.
Biomolecular structure
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Biomolecular structure is the intricate folded, three-dimensional shape that is formed by a molecule of protein, DNA, or RNA, and that is important to its function. The structure of molecules may be considered at any of several length scales ranging from the level of individual atoms to the relationships among entire protein subunits. This useful distinction among scales is often expressed as a decomposition of molecular structure into four levels, primary, secondary, tertiary, the scaffold for this multiscale organization of the molecule arises at the secondary level, where the fundamental structural elements are the molecules various hydrogen bonds. The terms primary, secondary, tertiary, and quaternary structure were introduced by Kaj Ulrik Linderstrøm-Lang in his 1951 Lane Medical Lectures at Stanford University, the primary structure of a biopolymer is the exact specification of its atomic composition and the chemical bonds connecting those atoms. For a typical unbranched, un-crosslinked biopolymer, the structure is equivalent to specifying the sequence of its monomeric subunits. Primary structure is sometimes mistakenly termed primary sequence, but there is no such term, the primary structure of a nucleic acid molecule refers to the exact sequence of nucleotides that comprise the whole molecule. Often, the primary structure encodes motifs that are of functional importance. The secondary structure is the pattern of hydrogen bonds in a biopolymer, secondary structure is formally defined by the hydrogen bonds of the biopolymer, as observed in an atomic-resolution structure. In proteins, the structure is defined by patterns of hydrogen bonds between backbone amide and carboxyl groups, where the DSSP definition of a hydrogen bond is used. In nucleic acids, the structure is defined by the hydrogen bonding between the nitrogenous bases. For proteins, however, the bonding is correlated with other structural features. Many other less formal definitions have been proposed, often applying concepts from the geometry of curves, such as curvature. Structural biologists solving a new structure will sometimes assign its secondary structure by eye. The secondary structure of an acid molecule refers to the base pairing interactions within one molecule or set of interacting molecules. The secondary structure of biological RNAs can often be uniquely decomposed into stems, often, these elements or combinations of them can be further classified, e. g. tetraloops, pseudoknots and stem-loops. There are many secondary structure elements of importance to biological RNAs. Famous examples include the Rho-independent terminator stem-loops and the transfer RNA cloverleaf, there is a minor industry of researchers attempting to determine the secondary structure of RNA molecules. Approaches include both experimental and computational methods, the tertiary structure of a protein or any other macromolecule is its three-dimensional structure, as defined by the atomic coordinates
19.
Molecule
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A molecule is an electrically neutral group of two or more atoms held together by chemical bonds. Molecules are distinguished from ions by their lack of electrical charge, however, in quantum physics, organic chemistry, and biochemistry, the term molecule is often used less strictly, also being applied to polyatomic ions. In the kinetic theory of gases, the molecule is often used for any gaseous particle regardless of its composition. According to this definition, noble gas atoms are considered molecules as they are in fact monoatomic molecules. A molecule may be homonuclear, that is, it consists of atoms of one element, as with oxygen, or it may be heteronuclear. Atoms and complexes connected by non-covalent interactions, such as hydrogen bonds or ionic bonds, are not considered single molecules. Molecules as components of matter are common in organic substances and they also make up most of the oceans and atmosphere. Also, no typical molecule can be defined for ionic crystals and covalent crystals, the theme of repeated unit-cellular-structure also holds for most condensed phases with metallic bonding, which means that solid metals are also not made of molecules. In glasses, atoms may also be together by chemical bonds with no presence of any definable molecule. The science of molecules is called molecular chemistry or molecular physics, in practice, however, this distinction is vague. In molecular sciences, a molecule consists of a system composed of two or more atoms. Polyatomic ions may sometimes be thought of as electrically charged molecules. The term unstable molecule is used for very reactive species, i. e, according to Merriam-Webster and the Online Etymology Dictionary, the word molecule derives from the Latin moles or small unit of mass. Molecule – extremely minute particle, from French molécule, from New Latin molecula, diminutive of Latin moles mass, a vague meaning at first, the vogue for the word can be traced to the philosophy of Descartes. The definition of the molecule has evolved as knowledge of the structure of molecules has increased, earlier definitions were less precise, defining molecules as the smallest particles of pure chemical substances that still retain their composition and chemical properties. Molecules are held together by covalent bonding or ionic bonding. Several types of non-metal elements exist only as molecules in the environment, for example, hydrogen only exists as hydrogen molecule. A molecule of a compound is made out of two or more elements, a covalent bond is a chemical bond that involves the sharing of electron pairs between atoms
20.
Protein domain
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A protein domain is a conserved part of a given protein sequence and structure that can evolve, function, and exist independently of the rest of the protein chain. Each domain forms a compact structure and often can be independently stable. Many proteins consist of structural domains. One domain may appear in a variety of different proteins, molecular evolution uses domains as building blocks and these may be recombined in different arrangements to create proteins with different functions. Domains vary in length from between about 25 amino acids up to 500 amino acids in length, the shortest domains such as zinc fingers are stabilized by metal ions or disulfide bridges. Domains often form functional units, such as the calcium-binding EF hand domain of calmodulin, because they are independently stable, domains can be swapped by genetic engineering between one protein and another to make chimeric proteins. The concept of the domain was first proposed in 1973 by Wetlaufer after X-ray crystallographic studies of hen lysozyme and papain, Wetlaufer defined domains as stable units of protein structure that could fold autonomously. In the past domains have been described as units of, compact structure function and evolution folding, each definition is valid and will often overlap, i. e. a compact structural domain that is found amongst diverse proteins is likely to fold independently within its structural environment. Nature often brings several domains together to form multidomain and multifunctional proteins with a vast number of possibilities, in a multidomain protein, each domain may fulfill its own function independently, or in a concerted manner with its neighbours. An appropriate example is pyruvate kinase, an enzyme that plays an important role in regulating the flux from fructose-1. It contains an all-β nucleotide binding domain, a binding domain. Each domain in this protein occurs in diverse sets of protein families, the central α/β-barrel substrate binding domain is one of the most common enzyme folds. It is seen in different enzyme families catalysing completely unrelated reactions. The α/β-barrel is commonly called the TIM barrel named after triose phosphate isomerase and it is currently classified into 26 homologous families in the CATH domain database. The TIM barrel is formed from a sequence of β-α-β motifs closed by the first and last strand hydrogen bonding together, there is debate about the evolutionary origin of this domain. One study has suggested that a single ancestral enzyme could have diverged into several families, the TIM-barrel in pyruvate kinase is discontinuous, meaning that more than one segment of the polypeptide is required to form the domain. This is likely to be the result of the insertion of one domain into another during the proteins evolution and it has been shown from known structures that about a quarter of structural domains are discontinuous. The inserted β-barrel regulatory domain is continuous, made up of a stretch of polypeptide
21.
Catalysis
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Catalysis is the increase in the rate of a chemical reaction due to the participation of an additional substance called a catalyst. In most cases, reactions occur faster with a catalyst because they require less activation energy, furthermore, since they are not consumed in the catalyzed reaction, catalysts can continue to act repeatedly. Often only tiny amounts are required in principle, in the presence of a catalyst, less free energy is required to reach the transition state, but the total free energy from reactants to products does not change. A catalyst may participate in multiple chemical transformations, the effect of a catalyst may vary due to the presence of other substances known as inhibitors or poisons or promoters. Catalyzed reactions have an activation energy than the corresponding uncatalyzed reaction, resulting in a higher reaction rate at the same temperature. However, the mechanics of catalysis is complex. Usually, the catalyst participates in this slowest step, and rates are limited by amount of catalyst, in heterogeneous catalysis, the diffusion of reagents to the surface and diffusion of products from the surface can be rate determining. A nanomaterial-based catalyst is an example of a heterogeneous catalyst, analogous events associated with substrate binding and product dissociation apply to homogeneous catalysts. Although catalysts are not consumed by the reaction itself, they may be inhibited, deactivated, in heterogeneous catalysis, typical secondary processes include coking where the catalyst becomes covered by polymeric side products. Additionally, heterogeneous catalysts can dissolve into the solution in a system or sublimate in a solid–gas system. The production of most industrially important chemicals involves catalysis, similarly, most biochemically significant processes are catalysed. Research into catalysis is a field in applied science and involves many areas of chemistry, notably organometallic chemistry. Catalysis is relevant to aspects of environmental science, e. g. the catalytic converter in automobiles. Many transition metals and transition metal complexes are used in catalysis as well, Catalysts called enzymes are important in biology. A catalyst works by providing a reaction pathway to the reaction product. The rate of the reaction is increased as this route has a lower activation energy than the reaction route not mediated by the catalyst. The disproportionation of hydrogen peroxide creates water and oxygen, as shown below,2 H2O2 →2 H2O + O2 This reaction is preferable in the sense that the reaction products are more stable than the starting material, though the uncatalysed reaction is slow. In fact, the decomposition of hydrogen peroxide is so slow that hydrogen peroxide solutions are commercially available and this reaction is strongly affected by catalysts such as manganese dioxide, or the enzyme peroxidase in organisms
22.
N-terminus
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The N-terminus is the start of a protein or polypeptide terminated by an amino acid with a free amine group. By convention, peptide sequences are written N-terminus to C-terminus, left to right in LTR languages and this correlates the translation direction to the text direction. Each amino acid has a group and a carboxylic group. The chain has two ends - an amine group, the N-terminus, and a carboxyl group, the C-terminus. When a protein is translated from messenger RNA, it is created from N-terminus to C-terminus, the amino end of an amino acid during the elongation stage of translation, attaches to the carboxyl end of the growing chain. Since the start codon of the genetic codes for the amino acid methionine. However, some proteins are modified posttranslationally, for example, by cleavage from a protein precursor, the N-terminus is the first part of the protein that exits the ribosome during protein biosynthesis. It often contains signal peptide sequences, intracellular postal codes that direct delivery of the protein to the proper organelle, the signal peptide is typically removed at the destination by a signal peptidase. The N-terminal amino acid of a protein is an important determinant of its half-life and this is called the N-end rule. The N-terminal signal peptide is recognized by the signal recognition particle, in eukaryotic cells, these proteins are synthesized at the rough endoplasmic reticulum. In prokaryotic cells, the proteins are exported across the cell membrane, in chloroplasts, signal peptides target proteins to the thylakoids. The N-terminal mitochondrial targeting peptide allows for the protein to be imported into the mitochondrion, the N-terminal chloroplast targeting peptide allows for the protein to be imported into the chloroplast. Protein N-termini can be modified co - or posttranslationally and it has been suggested that N-terminal acetylation can prevent a protein from following a secretory pathway. The N-terminus can be modified by the addition of a myristoyl anchor, proteins that are modified this way contain a consensus motif at their N-terminus as a modification signal. The N-terminus can also be modified by the addition of a fatty acid anchor to form N-acylated proteins, the most common form of such modification is the addition of a palmitoyl group. TopFIND, a database covering proteases, their cleavage site specificity, substrates, inhibitors
23.
Protein folding
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It is the physical process by which a polypeptide folds into its characteristic and functional three-dimensional structure from random coil. Each protein exists as a polypeptide or random coil when translated from a sequence of mRNA to a linear chain of amino acids. This polypeptide lacks any stable three-dimensional structure, as the polypeptide chain is being synthesized by the ribosome, the linear chain begins to fold into its three dimensional structure. Folding begins to occur even during translation of the polypeptide chain, amino acids interact with each other to produce a well-defined three-dimensional structure, the folded protein, known as the native state. The resulting three-dimensional structure is determined by the amino acid sequence or primary structure, the energy landscape describes the folding pathways in which the unfolded protein is able to assume its native state. Experiments beginning in the 1980s indicate the codon for an acid can also influence protein structure. The correct three-dimensional structure is essential to function, although parts of functional proteins may remain unfolded. Failure to fold into native structure generally produces inactive proteins, several neurodegenerative and other diseases are believed to result from the accumulation of amyloid fibrils formed by misfolded proteins. Many allergies are caused by folding of some proteins, because the immune system does not produce antibodies for certain protein structures. The primary structure of a protein, its linear amino-acid sequence, the amino acid composition is not as important as the sequence. The essential fact of folding, however, remains that the amino acid sequence of protein contains the information that specifies both the native structure and the pathway to attain that state. This is not to say that nearly identical amino acid sequences always fold similarly, conformations differ based on environmental factors as well, similar proteins fold differently based on where they are found. Formation of a structure is the first step in the folding process that a protein takes to assume its native structure. Formation of intramolecular hydrogen bonds provides another important contribution to protein stability, alpha helices are formed by hydrogen bonding of the backbone to form a spiral shape. The beta pleated sheet is a structure forms with the backbone bending over itself to form the hydrogen bonds. The hydrogen bonds are between the hydrogen and carbonyl carbon of the peptide bond. The alpha helices and beta pleated sheets can be amphipathic in nature, or contain a hydrophilic portion, secondary structure hierarchically gives way to tertiary structure formation. Tertiary structure of a protein involves a single chain, however
24.
Protein biosynthesis
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Protein synthesis is the process whereby biological cells generate new proteins, it is balanced by the loss of cellular proteins via degradation or export. Protein biosynthesis is regulated at multiple steps. They are principally during transcription and translation, the cistron DNA is transcribed into the first of a series of RNA intermediates. The last version is used as a template in synthesis of a polypeptide chain, Protein will often be synthesized directly from genes by translating mRNA. However, when a protein must be available on short notice or in large quantities, a proprotein is an inactive protein containing one or more inhibitory peptides that can be activated when the inhibitory sequence is removed by proteolysis during posttranslational modification. A preprotein is a form that contains a sequence that specifies its insertion into or through membranes. The signal peptide is cleaved off in the endoplasmic reticulum, preproproteins have both sequences still present. The amino acids are linked together to extend the growing protein chain. This whole complex of processes is carried out by the ribosome, the ribosome latches onto the end of an mRNA molecule and moves along it, capturing loaded tRNA molecules and joining together their amino acids to form a new protein chain. Protein biosynthesis, although similar, is different for prokaryotes and eukaryotes. In transcription an mRNA chain is generated, with one strand of the DNA double helix in the genome as a template and this strand is called the template strand. Transcription occurs in the nucleus, where the DNA is held. The DNA structure of the cell is made up of two made up of sugar and phosphate held together by hydrogen bonds between the bases of opposite strands. The sugar and the phosphate in each strand are joined together by stronger covalent bonds. The DNA is unzipped by the helicase, leaving the single nucleotide chain open to be copied. RNA polymerase reads the DNA strand from the 3-prime end to the 5-prime end, the general RNA structure is very similar to the DNA structure, but in RNA the nucleotide uracil takes the place that thymine occupies in DNA. The single strand of mRNA leaves the nucleus through nuclear pores, hnRNA then undergoes splicing of introns via spliceosomes to produce the final mRNA. The synthesis of proteins from RNA is known as translation, in eukaryotes, translation occurs in the cytoplasm, where the ribosomes are located
25.
Nicotinamide adenine dinucleotide
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Nicotinamide adenine dinucleotide is a coenzyme found in all living cells. The compound is a dinucleotide, because it consists of two nucleotides joined through their phosphate groups, one nucleotide contains an adenine base and the other nicotinamide. Nicotinamide adenine dinucleotide exists in two forms, an oxidized and reduced form abbreviated as NAD+ and NADH respectively, in metabolism, nicotinamide adenine dinucleotide is involved in redox reactions, carrying electrons from one reaction to another. The coenzyme is, therefore, found in two forms in cells, NAD+ is an oxidizing agent – it accepts electrons from other molecules and becomes reduced and this reaction forms NADH, which can then be used as a reducing agent to donate electrons. These electron transfer reactions are the function of NAD. However, it is used in other cellular processes, the most notable one being a substrate of enzymes that add or remove chemical groups from proteins. Because of the importance of these functions, the involved in NAD metabolism are targets for drug discovery. In organisms, NAD can be synthesized from simple building-blocks from the amino acids tryptophan or aspartic acid, in an alternative fashion, more complex components of the coenzymes are taken up from food as the vitamin called niacin. Similar compounds are released by reactions that break down the structure of NAD and these preformed components then pass through a salvage pathway that recycles them back into the active form. Some NAD is also converted into nicotinamide adenine dinucleotide phosphate, the chemistry of this related coenzyme is similar to that of NAD, nicotinamide adenine dinucleotide, like all dinucleotides, consists of two nucleosides joined by a pair of bridging phosphate groups. The nucleosides each contain a ring, one with adenine attached to the first carbon atom. The nicotinamide moiety can be attached in two orientations to this carbon atom. Because of these two structures, the compound exists as two diastereomers. It is the diastereomer of NAD+ that is found in organisms. These nucleotides are joined together by a bridge of two groups through the 5 carbons. In metabolism, the compound accepts or donates electrons in redox reactions, such reactions involve the removal of two hydrogen atoms from the reactant, in the form of a hydride ion, and a proton. The proton is released into solution, while the reductant RH2 is oxidized, the midpoint potential of the NAD+/NADH redox pair is −0.32 volts, which makes NADH a strong reducing agent. The reaction is reversible, when NADH reduces another molecule and is re-oxidized to NAD+
26.
Diphthamide
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Diphthamide is a post-translationally modified histidine amino acid found in archaeal and eukaryotic elongation factor 2. Diphthamide is proposed to be a 2-[3-carboxyamido-3-propyl histidine, though this structure has been confirmed by X-ray crystallography, its stereochemistry is uncertain. The presence or absence of diphthamide is known to affect NF-κB or death receptor pathways, diphthamide is biosynthesized from histidine and S-adenosyl methionine
27.
EEF2
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Eukaryotic elongation factor 2 is a protein that in humans is encoded by the EEF2 gene. This gene encodes a member of the GTP-binding translation elongation factor family and this protein is an essential factor for protein synthesis. It promotes the GTP-dependent translocation of the ribosome and this protein is completely inactivated by EF-2 kinase phosphorylation. It is the target of diphtheria toxin, and exotoxin A, the inactivation of EF-2 by toxins inhibits protein production in the host, causing symptoms due to loss of function in affected cells. Peptide Elongation Factor 2 at the US National Library of Medicine Medical Subject Headings
28.
Globin
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The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments, two prominent members include myoglobin and hemoglobin. Both of these proteins reversibly bind oxygen via a prosthetic group. They are widely distributed in many organisms, globin superfamily members share a common three-dimensional fold. This globin fold typically consists of eight alpha helices, although some proteins have additional helix extensions at their termini, since the globin fold contains only helices, it is classified as an all-alpha protein fold. The globin fold is found in its namesake globin families as well as in phycocyanins, the globin fold was thus the first protein fold discovered. The eight helices of the globin fold core share significant nonlocal structure, the helices pack together at an average angle of about 50 degrees, significantly steeper than other helical packings such as the helix bundle. Globins evolved from an ancestor and can be divided into three groups, single-domain globins, and two types of chimeric globins, flavohaemoglobins and globin-coupled sensors. Bacteria have all three types of globins, while archaea lack flavohaemoglobins, and eukaryotes lack globin-coupled sensors, several functionally different haemoglobins can coexist in the same species. Eight globins are known to occur in vertebrates, androglobin, cytoglobin, globin E, globin X, globin Y, although the fold of the globin superfamily is highly evolutionarily conserved, the sequences that form the fold can have as low as 16% sequence identity. The most famous mutation in the fold is a change from glutamate to valine in one chain of the hemoglobin molecule. This mutation creates a patch on the protein surface that promotes intermolecular aggregation. Neuroglobin belongs to a branch of the family that diverged early in evolution. Cytoglobin, an oxygen sensor expressed in multiple tissues, erythrocruorin, highly cooperative extracellular respiratory proteins found in annelids and arthropods that are assembled from as many as 180 subunit into hexagonal bilayers. Leghaemoglobin, occurs in the nodules of leguminous plants, where it facilitates the diffusion of oxygen to symbiotic bacteriods in order to promote nitrogen fixation. Non-symbiotic haemoglobin, occurs in plants, and can be over-expressed in stressed plants. Flavohaemoglobins, chimeric, with an N-terminal globin domain and a C-terminal ferredoxin reductase-like NAD/FAD-binding domain, fHb provides protection against nitric oxide via its C-terminal domain, which transfers electrons to haem in the globin. They bind oxygen, and act to initiate a response or regulate gene expression
29.
Alpha helix
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This secondary structure is also sometimes called a classic Pauling–Corey–Branson α-helix. The name 3. 613-helix is also used for type of helix, denoting the average number of residues per helical turn. Among types of structure in proteins, the α-helix is the most regular. In the early 1930s, William Astbury showed that there were changes in the X-ray fiber diffraction of moist wool or hair fibers upon significant stretching. The data suggested that the unstretched fibers had a molecular structure with a characteristic repeat of ~5.1 ångströms. Astbury initially proposed a structure for the fibers. He later joined other researchers in proposing that, the protein molecules formed a helix the stretching caused the helix to uncoil. Hans Neurath was the first to show that Astburys models could not be correct in detail, neuraths paper and Astburys data inspired H. S. Taylor, Maurice Huggins and Bragg and collaborators to propose models of keratin that somewhat resemble the modern α-helix. The pivotal moment came in the spring of 1948, when Pauling caught a cold. Being bored, he drew a polypeptide chain of roughly correct dimensions on a strip of paper and folded it into a helix, after a few attempts, he produced a model with physically plausible hydrogen bonds. Pauling then worked with Corey and Branson to confirm his model before publication. The amino acids in an α-helix are arranged in a helical structure where each amino acid residue corresponds to a 100° turn in the helix. Dunitz describes how Paulings first article on the theme in fact shows a left-handed helix, short pieces of left-handed helix sometimes occur with a large content of achiral glycine amino acids, but are unfavorable for the other normal, biological L-amino acids. The pitch of the alpha-helix is 5.4 Å, which is the product of 1.5 and 3.6, the alpha-helices can be identified in protein structure using several computational methods, one of which being DSSP. Similar structures include the 310 helix and the π-helix, the subscripts refer to the number of atoms in the closed loop formed by the hydrogen bond. Residues in α-helices typically adopt backbone dihedral angles around, as shown in the image at right, in more general terms, they adopt dihedral angles such that the ψ dihedral angle of one residue and the φ dihedral angle of the next residue sum to roughly -105°. As a consequence, α-helical dihedral angles, in general, fall on a stripe on the Ramachandran diagram. For comparison, the sum of the angles for a 310 helix is roughly -75°
30.
Helix
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A helix is a type of smooth space curve, i. e. a curve in three-dimensional space. It has the property that the tangent line at any point makes a constant angle with a line called the axis. Examples of helices are coil springs and the handrails of spiral staircases, a filled-in helix – for example, a spiral ramp – is called a helicoid. Helices are important in biology, as the DNA molecule is formed as two intertwined helices, and many proteins have helical substructures, known as alpha helices, the word helix comes from the Greek word ἕλιξ, twisted, curved. Helices can be either right-handed or left-handed, handedness is a property of the helix, not of the perspective, a right-handed helix cannot be turned to look like a left-handed one unless it is viewed in a mirror, and vice versa. Most hardware screw threads are right-handed helices, the alpha helix in biology as well as the A and B forms of DNA are also right-handed helices. The Z form of DNA is left-handed, the pitch of a helix is the height of one complete helix turn, measured parallel to the axis of the helix. A double helix consists of two helices with the axis, differing by a translation along the axis. A conic helix may be defined as a spiral on a conic surface, an example is the Corkscrew roller coaster at Cedar Point amusement park. A circular helix, has constant band curvature and constant torsion, a curve is called a general helix or cylindrical helix if its tangent makes a constant angle with a fixed line in space. A curve is a general helix if and only if the ratio of curvature to torsion is constant, a curve is called a slant helix if its principal normal makes a constant angle with a fixed line in space. It can be constructed by applying a transformation to the frame of a general helix. Some curves found in nature consist of multiple helices of different handedness joined together by transitions known as tendril perversions, in mathematics, a helix is a curve in 3-dimensional space. The following parametrisation in Cartesian coordinates defines a particular helix, Probably the simplest equations for one is x = cos , y = sin , z = t. As the parameter t increases, the point traces a right-handed helix of pitch 2θ and radius 1 about the z-axis, in cylindrical coordinates, the same helix is parametrised by, r =1, θ = t, h = t. A circular helix of radius a and slope b/a is described by the following parametrisation, another way of mathematically constructing a helix is to plot the complex-valued function exi as a function of the real number x. The value of x and the real and imaginary parts of the function value give this plot three real dimensions, except for rotations, translations, and changes of scale, all right-handed helices are equivalent to the helix defined above. The equivalent left-handed helix can be constructed in a number of ways, in music, pitch space is often modeled with helices or double helices, most often extending out of a circle such as the circle of fifths, so as to represent octave equivalency
31.
Cell membrane
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The cell membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is permeable to ions and organic molecules and controls the movement of substances in. The basic function of the membrane is to protect the cell from its surroundings. It consists of the bilayer with embedded proteins. Cell membranes can be artificially reassembled, Some authors that did not believe that there was a functional permeable boundary at the surface of the cell preferred to use the term plasmalemma to the extern region of the cell. The cell membrane surrounds the cytoplasm of living cells, physically separating the components from the extracellular environment. The cell membrane also plays a role in anchoring the cytoskeleton to provide shape to the cell, fungi, bacteria, most archaea, and plants also have a cell wall, which provides a mechanical support to the cell and precludes the passage of larger molecules. The cell membrane is permeable and able to regulate what enters and exits the cell. The movement of substances across the membrane can be passive, occurring without the input of cellular energy, or active. The membrane also maintains the cell potential, the cell membrane thus works as a selective filter that allows only certain things to come inside or go outside the cell. The cell employs a number of mechanisms that involve biological membranes,1. Passive osmosis and diffusion, Some substances such as carbon dioxide and oxygen, can move across the membrane by diffusion. Because the membrane acts as a barrier for certain molecules and ions, such a concentration gradient across a semipermeable membrane sets up an osmotic flow for the water. Transmembrane protein channels and transporters, Nutrients, such as sugars or amino acids, must enter the cell, such molecules diffuse passively through protein channels such as aquaporins in facilitated diffusion or are pumped across the membrane by transmembrane transporters. Protein channel proteins, also called permeases, are quite specific, recognizing and transporting only a limited food group of chemical substances. Endocytosis, Endocytosis is the process in which cells absorb molecules by engulfing them, the plasma membrane creates a small deformation inward, called an invagination, in which the substance to be transported is captured. The deformation then pinches off from the membrane on the inside of the cell, Endocytosis is a pathway for internalizing solid particles, small molecules and ions, and macromolecules. Endocytosis requires energy and is thus a form of active transport and this is the process of exocytosis
32.
PH
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In chemistry, pH is a numeric scale used to specify the acidity or basicity of an aqueous solution. It is approximately the negative of the base 10 logarithm of the concentration, measured in units of moles per liter. More precisely it is the negative of the logarithm to base 10 of the activity of the hydrogen ion, solutions with a pH less than 7 are acidic and solutions with a pH greater than 7 are basic. Pure water is neutral, at pH7, being neither an acid nor a base, contrary to popular belief, the pH value can be less than 0 or greater than 14 for very strong acids and bases respectively. The pH scale is traceable to a set of standard solutions whose pH is established by international agreement, the pH of aqueous solutions can be measured with a glass electrode and a pH meter, or an indicator. In the first papers, the notation had the H as a subscript to the p, as so. The exact meaning of the p in pH is disputed, but according to the Carlsberg Foundation and it has also been suggested that the p stands for the German Potenz, others refer to French puissance. Another suggestion is that the p stands for the Latin terms pondus hydrogenii, potentia hydrogenii and it is also suggested that Sørensen used the letters p and q simply to label the test solution and the reference solution. Currently in chemistry, the p stands for decimal cologarithm of, PH is defined as the decimal logarithm of the reciprocal of the hydrogen ion activity, aH+, in a solution. P H = − log 10 = log 10 For example and this definition was adopted because ion-selective electrodes, which are used to measure pH, respond to activity. For H+ number of electrons transferred is one and it follows that electrode potential is proportional to pH when pH is defined in terms of activity. The reference electrode may be a silver chloride electrode or a calomel electrode, the hydrogen-ion selective electrode is a standard hydrogen electrode. Reference electrode | concentrated solution of KCl || test solution | H2 | Pt Firstly, the cell is filled with a solution of hydrogen ion activity. Then the emf, EX, of the cell containing the solution of unknown pH is measured. PH = pH + E S − E X z The difference between the two measured emf values is proportional to pH and this method of calibration avoids the need to know the standard electrode potential. The proportionality constant, 1/z is ideally equal to 12.303 R T / F the Nernstian slope, to apply this process in practice, a glass electrode is used rather than the cumbersome hydrogen electrode. A combined glass electrode has a reference electrode. It is calibrated against buffer solutions of hydrogen ion activity
33.
Endosome
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In cell biology, an endosome is a membrane-bound compartment inside eukaryotic cells. It is a compartment of the membrane transport pathway originating from the trans Golgi membrane. Molecules or ligands internalized from the membrane can follow this pathway all the way to lysosomes for degradation. Molecules are also transported to endosomes from the network and either continue to lysosomes or recycle back to the Golgi. Endosomes can be classified as early, sorting, or late depending on their stage post internalization, endosomes represent a major sorting compartment of the endomembrane system in cells. In HeLa cells, endosomes are approximately 500 nm in diameter when fully mature, endosomes provide an environment for material to be sorted before it reaches the degradative lysosome. For example, LDL is taken into the cell by binding to the LDL receptor at the cell surface, upon reaching early endosomes, the LDL dissociates from the receptor, and the receptor can be recycled to the cell surface. The LDL remains in the endosome and is delivered to lysosomes for processing, LDL dissociates because of the slightly acidified environment of the early endosome, generated by a vacuolar membrane proton pump V-ATPase. On the other hand, EGF and the EGF receptor have a pH-resistant bond that persists until it is delivered to lysosomes for their degradation, the mannose 6-phosphate receptor carries ligands from the Golgi destined for the lysosome by a similar mechanism. Endosomes comprise three different compartments, early endosomes, late endosomes, and recycling endosomes and they are distinguished by the time it takes for endocytosed material to reach them, and by markers such as rabs. Once endocytic vesicles have uncoated, they fuse with early endosomes, early endosomes then mature into late endosomes before fusing with lysosomes. Early endosomes mature in several ways to form late endosomes and they become increasingly acidic mainly through the activity of the V-ATPase. Many molecules that are recycled are removed by concentration in the regions of early endosomes. Loss of these tubules to recycling pathways means that late endosomes mostly lack tubules and they also increase in size due to the homotypic fusion of early endosomes into larger vesicles. Removal of recycling molecules such as receptors and mannose 6-phosphate receptors continues during this period. Finally, the endosomes lose RAB5A and acquire RAB7A, making them competent for fusion with lysosomes, fusion of late endosomes with lysosomes has been shown to result in the formation of a hybrid compartment, with characteristics intermediate of the two source compartments. For example, lysosomes are more dense than late endosomes, lysosomes reform by recondensation to their normal, higher density. However, before this happens, more late endosomes may fuse with the hybrid, some material recycles to the plasma membrane directly from early endosomes, but most traffics via recycling endosomes
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Cytoplasm
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In cell biology, the cytoplasm is the material within a living cell, excluding the cell nucleus. It comprises cytosol and the organelles – the cells internal sub-structures, all of the contents of the cells of prokaryotic organisms are contained within the cytoplasm. Within the cells of organisms the contents of the cell nucleus are separated from the cytoplasm. The cytoplasm is about 80% water and usually colorless, the submicroscopic ground cell substance or cytoplasmatic matrix which remains after exclusion the cell organelles and particles is groundplasm. It is within the cytoplasm that most cellular activities occur, such as many metabolic pathways including glycolysis, the concentrated inner area is called the endoplasm and the outer layer is called the cell cortex or the ectoplasm. Movement of calcium ions in and out of the cytoplasm is an activity for metabolic processes. In plants, movement of the cytoplasm around vacuoles is known as cytoplasmic streaming, the term was introduced by Rudolf von Kölliker in 1863, originally as a synonym for protoplasm, but later it has come to mean the cell substance and organelles outside the nucleus. There has been disagreement on the definition of cytoplasm, as some authors prefer to exclude from it some organelles. The physical properties of the cytoplasm have been contested in recent years and it remains uncertain how the varied components of the cytoplasm interact to allow movement of particles and organelles while maintaining the cell’s structure. The flow of cytoplasmic components plays an important role in cellular functions which are dependent on the permeability of the cytoplasm. An example of function is cell signalling, a process which is dependent on the manner in which signaling molecules are allowed to diffuse across the cell. While small signaling molecules like calcium ions are able to diffuse with ease, larger molecules, the irregular dynamics of such particles have given rise to various theories on the nature of the cytoplasm. There has long been evidence that the cytoplasm behaves like a sol-gel and it is thought that the component molecules and structures of the cytoplasm behave at times like a disordered colloidal solution and at other times like an integrated network, forming a solid mass. Recently it has proposed that the cytoplasm behaves like a glass-forming liquid approaching the glass transition. A cells ability to vitrify in the absence of activity, as in dormant periods. There has been examining the motion of cytoplasmic particles independent of the nature of the cytoplasm. In such an approach, the aggregate random forces within the cell caused by motor proteins explain the non-Brownian motion of cytoplasmic constituents. The three major elements of the cytoplasm are the cytosol, organelles and inclusions, the cytosol is the portion of the cytoplasm not contained within membrane-bound organelles
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C-terminus
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The C-terminus is the end of an amino acid chain, terminated by a free carboxyl group. When the protein is translated from messenger RNA, it is created from N-terminus to C-terminus, the convention for writing peptide sequences is to put the C-terminal end on the right and write the sequence from N- to C-terminus. Each amino acid has a group and an amine group. Amino acids link to one another to form a chain by a reaction which joins the amine group of one amino acid to the carboxyl group of the next. Thus polypeptide chains have an end with a carboxyl group, the C-terminus, and an end with an unbound amine group. Proteins are naturally synthesized starting from the N-terminus and ending at the C-terminus, while the N-terminus of a protein often contains targeting signals, the C-terminus can contain retention signals for protein sorting. The most common ER retention signal is the amino acid sequence -KDEL or -HDEL at the C-terminus and this keeps the protein in the endoplasmic reticulum and prevents it from entering the secretory pathway. One form of C-terminal modification is prenylation, during prenylation, a farnesyl- or geranylgeranyl-isoprenoid membrane anchor is added to a cysteine residue near the C-terminus. Small, membrane-bound G proteins are modified this way. Another form of C-terminal modification is the addition of a phosphoglycan, glycosylphosphatidylinositol, the GPI anchor is attached to the C-terminus after proteolytic cleavage of a C-terminal propeptide. The most prominent example for this type of modification is the prion protein, the C-terminal domain of some proteins has specialized functions. In humans, the CTD of RNA polymerase II typically consists of up to 52 repeats of the sequence Tyr-Ser-Pro-Thr-Ser-Pro-Ser and this allows other proteins to bind to the C-terminal domain of RNA polymerase in order to activate polymerase activity. These domains then involved in the initiation of DNA transcription, the capping of the RNA transcript, N-terminus TopFIND, a scientific database covering proteases, their cleavage site specificity, substrates, inhibitors and protein termini originating from their activity
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Beta-sandwich
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β-sandwich domains consisting of 80 to 350 amino acids occur commonly in proteins. They are characterized by two opposing antiparallel β-sheets, the number of strands found in such domains may differ from one protein to another. β-sandwich domains are subdivided in a variety of different folds, the immunoglobulin-type fold found in antibodies consists of a sandwich arrangement of 7 and 9 antiparallel β-strands arranged in two β-sheets with a Greek-key topology. The Greek-key topology is also found in Human Transthyretin, the L-type lectin domain is a variation of the jelly roll fold. The C2 domain in its version is a β-sandwich composed of 8 β-strands
. PMID 12117903.
